Our goal is to understand the molecular pathway leading to programmed cell death in C. elegans. Naturally occurring or programmed cell deaths play an important role in animal development and homeostasis. Such deaths, which remove cells that are not needed or are potentially dangerous, are observed in a wide variety of tissues in both vertebrates and invertebrates. Proper control of programmed cell death is very important: breakdown in the regulation of this process appears to be associated with several types of cancer, autoimmunity and possibly neurodegenerative diseases. Recent studies by us and others have established that the genetic pathway for programmed cell death found in C. elegans is conserved and also functions in mammals. Thus, knowledge gained about nematode programmed cell death will further understanding of this phenomenon in humans. We have recently undertaken an in-depth study of programmed cell death in the germ line of C. elegans. The germ line tissue offers a number of advantages over the C. elegans soma, including a more vertebrate-like regulation of proliferation and the possibility of isolating significant amounts of dying cells for biochemical analysis. Our preliminary studies indicate that programmed cell death is a major - albeit so far mostly ignored - cell fate in the germ line and that many, but not all, of the genes involved in programmed cell death in the soma also function in the germ line. To further our understanding of the molecular mechanisms that lead to programmed cell death in the germ line, we will: 1) Determine how known genes affect the germ line deaths. 2) Identify and genetically characterize new genes that affect programmed cell death in the germ line. 3) Clone and molecularly characterize genes affecting germ line programmed cell death. 4) Use the C. elegans germ line for pharmacological and biochemical studies of programmed cell death. 5) Determine how environmental conditions modulate cell death in the C. elegans germ line. These studies will increase our knowledge of the molecular mechanism of programmed cell death in C. elegans. The similarities between the cell death pathway in nematodes and mammals suggest that our studies will also identify candidate genes involved in the regulation and execution of programmed cell death in humans.